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Mol Biol Cell. 2012 Apr;23(8):1435-45. doi: 10.1091/mbc.E11-09-0784. Epub 2012 Feb 22.

Reduced expression of MECP2 affects cell commitment and maintenance in neurons by triggering senescence: new perspective for Rett syndrome.

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1
Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, 80138 Naples, Italy.

Abstract

MECP2 protein binds preferentially to methylated CpGs and regulates gene expression by causing changes in chromatin structure. The mechanism by which impaired MECP2 activity can induce pathological abnormalities in the nervous system of patients with Rett syndrome (RTT) is not clearly understood. To gain further insight into the role of MECP2 in human neurogenesis, we compared the neural differentiation process in mesenchymal stem cells (MSCs) obtained from a RTT patient and from healthy donors. We further analyzed neural differentiation in a human neuroblastoma cell line carrying a partially silenced MECP2 gene. Senescence and reduced expression of neural markers were observed in proliferating and differentiating MSCs from the RTT patient, which suggests that impaired activity of MECP2 protein may impair neural differentiation, as observed in RTT patients. Next, we used an inducible expression system to silence MECP2 in neuroblastoma cells before and after the induction of neural differentiation via retinoic acid treatment. This approach was used to test whether MECP2 inactivation affected the cell fate of neural progenitors and/or neuronal differentiation and maintenance. Overall, our data suggest that neural cell fate and neuronal maintenance may be perturbed by senescence triggered by impaired MECP2 activity either before or after neural differentiation.

PMID:
22357617
PMCID:
PMC3327309
DOI:
10.1091/mbc.E11-09-0784
[Indexed for MEDLINE]
Free PMC Article
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